PMID- 21854392 OWN - NLM STAT- MEDLINE DCOM- 20111115 LR - 20191210 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 119 IP - 2 DP - 2011 Oct TI - Chronic psychosocial stress enhances long-term depression in a subthreshold amyloid-beta rat model of Alzheimer's disease. PG - 408-16 LID - 10.1111/j.1471-4159.2011.07437.x [doi] AB - In addition to genetic aspects, environmental factors such as stress may also play a critical role in the etiology of the late onset, sporadic Alzheimer's disease (AD). The present study examined the effect of chronic psychosocial stress in a sub-threshold Abeta (subAbeta) rat model of AD on long-term depression by two techniques: electrophysiological recordings of synaptic plasticity in anesthetized rats, and immunoblot analysis of memory- and AD-related signaling molecules. Chronic psychosocial stress was induced using a rat intruder model. The subAbeta rat model of AD, which was intended to represent outwardly normal individuals with a pre-disposition to AD, was induced by continuous infusion of 160 pmol/day Abeta(1)(-)(4)(2) via a 14-day i.c.v. osmotic pump. Results from electrophysiological recordings showed that long-term depression evoked in stress/subAbeta animals was significantly enhanced compared with that in animals exposed to stress or subAbeta infusion alone. Molecular analysis of various signaling molecules 1 h after induction of long-term depression revealed an increase in the levels of calcineurin and phosphorylated CaMKII in groups exposed to stress compared with other groups. The levels of the brain-derived neurotrophic factor (BDNF) were significantly decreased in stress/subAbeta animals but not in stress or subAbeta animals. In addition, the levels of beta-site amyloid precursor protein cleaving enzyme were markedly increased in stress/subAbeta. These findings suggest that chronic stress may accelerate the impairment of synaptic plasticity and consequently cognition in individuals 'at-risk' for AD. CI - (c) 2011 The Authors. Journal of Neurochemistry (c) 2011 International Society for Neurochemistry. FAU - Tran, Trinh T AU - Tran TT AD - Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas, USA. FAU - Srivareerat, Marisa AU - Srivareerat M FAU - Alhaider, Ibrahim A AU - Alhaider IA FAU - Alkadhi, Karim A AU - Alkadhi KA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110920 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Amyloid beta-Peptides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Peptide Fragments) RN - 0 (amyloid beta-protein (1-40)) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 3.1.3.16 (Calcineurin) RN - EC 3.4.- (Amyloid Precursor Protein Secretases) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.46 (Bace1 protein, rat) SB - IM MH - Alzheimer Disease/chemically induced/pathology/*psychology MH - Amyloid Precursor Protein Secretases/metabolism MH - Amyloid beta-Peptides/administration & dosage/*pharmacology MH - Animals MH - Aspartic Acid Endopeptidases/metabolism MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/metabolism MH - CA1 Region, Hippocampal/metabolism MH - Calcineurin/blood MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism MH - Chronic Disease MH - Depression/genetics/physiopathology/*psychology MH - Electrophysiological Phenomena MH - Hippocampus/pathology MH - Infusion Pumps, Implantable MH - Male MH - Peptide Fragments/administration & dosage/*pharmacology MH - Rats MH - Rats, Wistar MH - Risk MH - *Social Environment MH - Stress, Psychological/genetics/physiopathology/*psychology MH - Synaptic Transmission EDAT- 2011/08/23 06:00 MHDA- 2011/11/16 06:00 CRDT- 2011/08/23 06:00 PHST- 2011/08/23 06:00 [entrez] PHST- 2011/08/23 06:00 [pubmed] PHST- 2011/11/16 06:00 [medline] AID - 10.1111/j.1471-4159.2011.07437.x [doi] PST - ppublish SO - J Neurochem. 2011 Oct;119(2):408-16. doi: 10.1111/j.1471-4159.2011.07437.x. Epub 2011 Sep 20.